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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 11/2006

01-11-2006 | Original Article

Enhancement of anti-tumor immunity specific to murine glioma by vaccination with tumor cell lysate-pulsed dendritic cells engineered to produce interleukin-12

Authors: Chang-Hyun Kim, Min-Jung Hong, Sung-Dong Park, Choong-Kwon Kim, Mi-Young Park, Hyun-Jung Sohn, Hyun-Il Cho, Tai-Gyu Kim, Yong-Kil Hong

Published in: Cancer Immunology, Immunotherapy | Issue 11/2006

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Abstract

Aim: The aim of this study was to develop an immunotherapy specific to a malignant glioma by examining the efficacy of glioma tumor-specific cytotoxic T lymphocytes (CTL) as well as the anti-tumor immunity by vaccination with dendritic cells (DC) engineered to express murine IL-12 using adenovirus-mediated gene transfer and pulsed with a GL26 glioma cell lysate (AdVIL-12/DC+GL26) was investigated. Experimentl: For measuring CTL activity, splenocytes were harvested from the mice immunized with AdVIL-12/DC+GL26 and restimulated with syngeneic GL26 for 7 days. The frequencies of antigen-specific cytokine-secreting T cell were determined with mIFN-γ ELISPOT. The cytotoxicity of CTL was assessed in a standard 51Cr-release assay. For the protective study in the subcutaneous tumor model, the mice were vaccinated subcutaneously (s.c) with 1×106 AdVIL-12/DC+GL26 in the right flanks on day −21, −14 and −7. On day 7, the mice were challenged with 1×106 GL26 tumor cells in the shaved left flank. For a protective study in the intracranial tumor model, the mice were vaccinated with 1×106 AdVIL-12/DC+GL26 s.c in the right flanks on days −21, −14 and −7. Fresh 1×104 GL26 cells were inoculated into the brain on day 0. To prove a therapeutic benefit in established tumors, subcutaneous or intracranial GL26 tumor-bearing mice were vaccinated s.c with 1×106 AdVIL-12/DC+GL26 on day 5, 12 and 19 after tumor cell inoculation. Results: Splenocytes from the mice vaccinated with the AdVIL-12/DC+GL26 showed enhanced induction of tumor-specific CTL and increased numbers of IFN-γ: secreting T cells by ELISPOT. Moreover, vaccination of AdVIL-12/DC+GL26 enhanced the induction of anti-tumor immunity in both the subcutaneous and intracranial tumor models. Conclusions: These preclinical model results suggest that DC engineered to express IL-12 and pulsed with a tumor lysate could be used in a possible immunotherapeutic strategy for malignant glioma.
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Metadata
Title
Enhancement of anti-tumor immunity specific to murine glioma by vaccination with tumor cell lysate-pulsed dendritic cells engineered to produce interleukin-12
Authors
Chang-Hyun Kim
Min-Jung Hong
Sung-Dong Park
Choong-Kwon Kim
Mi-Young Park
Hyun-Jung Sohn
Hyun-Il Cho
Tai-Gyu Kim
Yong-Kil Hong
Publication date
01-11-2006
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 11/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0134-x

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